'Final common pathway' of human cancer immunotherapy: targeting random somatic mutations.

Abstract:

:Effective clinical cancer immunotherapies, such as administration of the cytokine IL-2, adoptive cell transfer (ACT) and the recent success of blockade of the checkpoint modulators CTLA-4 and PD-1, have been developed without clear identification of the immunogenic targets expressed by human cancers in vivo. Immunotherapy of patients with cancer through the use of ACT with autologous lymphocytes has provided an opportunity to directly investigate the antigen recognition of lymphocytes that mediate cancer regression in humans. High-throughput immunological testing of such lymphocytes in combination with improvements in deep sequencing of the autologous cancer have provided new insight into the molecular characterization and incidence of anti-tumor lymphocytes present in patients with cancer. Here we highlight evidence suggesting that T cells that target tumor neoantigens arising from cancer mutations are the main mediators of many effective cancer immunotherapies in humans.

journal_name

Nat Immunol

journal_title

Nature immunology

authors

Tran E,Robbins PF,Rosenberg SA

doi

10.1038/ni.3682

subject

Has Abstract

pub_date

2017-02-15 00:00:00

pages

255-262

issue

3

eissn

1529-2908

issn

1529-2916

pii

ni.3682

journal_volume

18

pub_type

杂志文章,评审
  • Id2 and Id3 maintain the regulatory T cell pool to suppress inflammatory disease.

    abstract::Regulatory T (Treg) cells suppress the development of inflammatory disease, but our knowledge of transcriptional regulators that control this function remains incomplete. Here we show that expression of Id2 and Id3 in Treg cells was required to suppress development of fatal inflammatory disease. We found that T cell a...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.2928

    authors: Miyazaki M,Miyazaki K,Chen S,Itoi M,Miller M,Lu LF,Varki N,Chang AN,Broide DH,Murre C

    更新日期:2014-08-01 00:00:00

  • Patterns of nonclassical MHC antigen presentation.

    abstract::The identification of pattern-recognition receptors that selectively respond to evolutionarily conserved chemical (often pathogen-derived) moieties has provided key insight into how innate immune cells facilitate rapid and relatively specific antimicrobial immune activity. In contrast, relatively slower adaptive immun...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni1475

    authors: Hansen TH,Huang S,Arnold PL,Fremont DH

    更新日期:2007-06-01 00:00:00

  • Serum amyloid A is a soluble pattern recognition receptor that drives type 2 immunity.

    abstract::The molecular basis for the propensity of a small number of environmental proteins to provoke allergic responses is largely unknown. Herein, we report that mite group 13 allergens of the fatty acid-binding protein (FABP) family are sensed by an evolutionarily conserved acute-phase protein, serum amyloid A1 (SAA1), tha...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/s41590-020-0698-1

    authors: Smole U,Gour N,Phelan J,Hofer G,Köhler C,Kratzer B,Tauber PA,Xiao X,Yao N,Dvorak J,Caraballo L,Puerta L,Rosskopf S,Chakir J,Malle E,Lane AP,Pickl WF,Lajoie S,Wills-Karp M

    更新日期:2020-07-01 00:00:00

  • Plasma cell differentiation and the unfolded protein response intersect at the transcription factor XBP-1.

    abstract::The transcription factor X-box binding protein 1 (XBP-1) is essential for the differentiation of plasma cells and the unfolded protein response (UPR). Here we show that UPR-induced splicing of XBP-1 by the transmembrane endonuclease IRE1 is required to restore production of immunoglobulin in XBP-1-/- mouse B cells, pr...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni907

    authors: Iwakoshi NN,Lee AH,Vallabhajosyula P,Otipoby KL,Rajewsky K,Glimcher LH

    更新日期:2003-04-01 00:00:00

  • STEEP mediates STING ER exit and activation of signaling.

    abstract::STING is essential for control of infections and for tumor immunosurveillance, but it can also drive pathological inflammation. STING resides on the endoplasmic reticulum (ER) and traffics following stimulation to the ERGIC/Golgi, where signaling occurs. Although STING ER exit is the rate-limiting step in STING signal...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/s41590-020-0730-5

    authors: Zhang BC,Nandakumar R,Reinert LS,Huang J,Laustsen A,Gao ZL,Sun CL,Jensen SB,Troldborg A,Assil S,Berthelsen MF,Scavenius C,Zhang Y,Windross SJ,Olagnier D,Prabakaran T,Bodda C,Narita R,Cai Y,Zhang CG,Stenmark H,Do

    更新日期:2020-08-01 00:00:00

  • Skewing of the population balance of lymphoid and myeloid cells by secreted and intracellular osteopontin.

    abstract::The balance of myeloid populations and lymphoid populations must be well controlled. Here we found that osteopontin (OPN) skewed this balance during pathogenic conditions such as infection and autoimmunity. Notably, two isoforms of OPN exerted distinct effects in shifting this balance through cell-type-specific regula...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.3791

    authors: Kanayama M,Xu S,Danzaki K,Gibson JR,Inoue M,Gregory SG,Shinohara ML

    更新日期:2017-09-01 00:00:00

  • Author Correction: Mechanosensing through immunoreceptors.

    abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

    journal_title:Nature immunology

    pub_type: 已发布勘误

    doi:10.1038/s41590-019-0545-4

    authors: Zhu C,Chen W,Lou J,Rittase W,Li K

    更新日期:2019-12-01 00:00:00

  • Unconventional topology of self peptide-major histocompatibility complex binding by a human autoimmune T cell receptor.

    abstract::Autoimmune diseases are caused by self-reactive lymphocytes that have escaped deletion. Here we have determined the structure of the trimolecular complex for a T cell receptor (TCR) from a patient with multiple sclerosis that causes autoimmunity in transgenic mice. The structure showed a TCR topology notably different...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni1187

    authors: Hahn M,Nicholson MJ,Pyrdol J,Wucherpfennig KW

    更新日期:2005-05-01 00:00:00

  • Fyn kinase initiates complementary signals required for IgE-dependent mast cell degranulation.

    abstract::Fc epsilon RI activation of mast cells is thought to involve Lyn and Syk kinases proximal to the receptor and the signaling complex organized by the linker for activation of T cells (LAT). We report here that Fc epsilon RI also uses a Fyn kinase-dependent pathway that does not require Lyn kinase or the adapter LAT for...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni817

    authors: Parravicini V,Gadina M,Kovarova M,Odom S,Gonzalez-Espinosa C,Furumoto Y,Saitoh S,Samelson LE,O'Shea JJ,Rivera J

    更新日期:2002-08-01 00:00:00

  • Pten inactivation alters peripheral B lymphocyte fate and reconstitutes CD19 function.

    abstract::Phosphoinositide 3-kinase (PI3K) and phosphatase and tensin homolog (PTEN) phosphatase serve essential functions in the regulation of cell growth, differentiation and survival by modulating intracellular phosphatidylinositol-3,4,5-trisphosphate (PI-3,4,5-P3) concentrations. Here we show that the conditional deletion o...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni892

    authors: Anzelon AN,Wu H,Rickert RC

    更新日期:2003-03-01 00:00:00

  • Distinct myeloid progenitor-differentiation pathways identified through single-cell RNA sequencing.

    abstract::According to current models of hematopoiesis, lymphoid-primed multi-potent progenitors (LMPPs) (Lin(-)Sca-1(+)c-Kit(+)CD34(+)Flt3(hi)) and common myeloid progenitors (CMPs) (Lin(-)Sca-1(+)c-Kit(+)CD34(+)CD41(hi)) establish an early branch point for separate lineage-commitment pathways from hematopoietic stem cells, wi...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.3412

    authors: Drissen R,Buza-Vidas N,Woll P,Thongjuea S,Gambardella A,Giustacchini A,Mancini E,Zriwil A,Lutteropp M,Grover A,Mead A,Sitnicka E,Jacobsen SEW,Nerlov C

    更新日期:2016-06-01 00:00:00

  • TRADD interacts with STAT1-alpha and influences interferon-gamma signaling.

    abstract::Tumor necrosis factor receptor 1 (TNFR1)-associated death domain protein (TRADD) is essential in recruiting signaling molecules to the TNFR1 receptor complex. Interferon-gamma (IFN-gamma) is a potent activator of macrophages and uses signal transducer and activator of transcription 1-alpha (STAT1-alpha) for signal tra...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni1025

    authors: Wesemann DR,Qin H,Kokorina N,Benveniste EN

    更新日期:2004-02-01 00:00:00

  • Upregulation of the CLIP self peptide on mature dendritic cells antagonizes T helper type 1 polarization.

    abstract::Dendritic cells (DCs) initiate and regulate immunity against foreign and self antigens. Here we identified more than 200 individual major histocompatibility complex class II-associated peptides on human DCs and found that mature DCs selectively upregulated the self peptide CLIP. CLIP cosegregated together with foreign...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni1108

    authors: Röhn TA,Boes M,Wolters D,Spindeldreher S,Müller B,Langen H,Ploegh H,Vogt AB,Kropshofer H

    更新日期:2004-09-01 00:00:00

  • Publisher Correction: Macrophages: damage control.

    abstract::In the version of this Research Highlight initially published, the url for the linked article was incorrect ( https://doi.org/10.1172/JCI90647JCI90647 ). The correct link is https://doi.org/10.1172/JCI90647 . The error has been corrected in the HTML and PDF versions of the article. ...

    journal_title:Nature immunology

    pub_type: 杂志文章,已发布勘误

    doi:10.1038/s41590-018-0159-2

    authors: Fehervari Z

    更新日期:2018-08-01 00:00:00

  • The kinase p38 activated by the metabolic regulator AMPK and scaffold TAB1 drives the senescence of human T cells.

    abstract::In T lymphocytes, the mitogen-activated protein kinase (MAPK) p38 regulates pleiotropic functions and is activated by canonical MAPK signaling or the alternative activation pathway downstream of the T cell antigen receptor (TCR). Here we found that senescent human T cells lacked the canonical and alternative pathways ...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.2981

    authors: Lanna A,Henson SM,Escors D,Akbar AN

    更新日期:2014-10-01 00:00:00

  • B lymphocytes from early vertebrates have potent phagocytic and microbicidal abilities.

    abstract::The present paradigm dictates that phagocytosis is accomplished mainly by 'professional' phagocytes (such as macrophages and monocytes), whereas B cells lack phagocytic capabilities. Here we demonstrate that B cells from teleost fish have potent in vitro and in vivo phagocytic activities. Particle uptake by B cells in...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni1389

    authors: Li J,Barreda DR,Zhang YA,Boshra H,Gelman AE,Lapatra S,Tort L,Sunyer JO

    更新日期:2006-10-01 00:00:00

  • Impaired assembly of the major histocompatibility complex class I peptide-loading complex in mice deficient in the oxidoreductase ERp57.

    abstract::The thiol-oxidoreductase ERp57 is an integral component of the peptide-loading complex of the major histocompatibility complex (MHC) class I pathway, but its function is unknown. To investigate its function in antigen presentation, we generated ERp57-deficient mice. Death in utero caused by ubiquitous ERp57 deletion w...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni1288

    authors: Garbi N,Tanaka S,Momburg F,Hämmerling GJ

    更新日期:2006-01-01 00:00:00

  • An intersection between the self-reactive regulatory and nonregulatory T cell receptor repertoires.

    abstract::The relationship between the T cell receptor (TCR) repertoires used by self-reactive transcription factor Foxp3-positive (Foxp3(+)) CD4(+) regulatory T cells (T(reg) cells) and nonregulatory T cells with autoimmune potential is unclear. Here we found that the TCR repertoire of thymic T(reg) cells in TCRbeta-transgenic...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni1318

    authors: Hsieh CS,Zheng Y,Liang Y,Fontenot JD,Rudensky AY

    更新日期:2006-04-01 00:00:00

  • High-density lipoprotein mediates anti-inflammatory reprogramming of macrophages via the transcriptional regulator ATF3.

    abstract::High-density lipoprotein (HDL) mediates reverse cholesterol transport and is known to be protective against atherosclerosis. In addition, HDL has potent anti-inflammatory properties that may be critical for protection against other inflammatory diseases. The molecular mechanisms of how HDL can modulate inflammation, p...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.2784

    authors: De Nardo D,Labzin LI,Kono H,Seki R,Schmidt SV,Beyer M,Xu D,Zimmer S,Lahrmann C,Schildberg FA,Vogelhuber J,Kraut M,Ulas T,Kerksiek A,Krebs W,Bode N,Grebe A,Fitzgerald ML,Hernandez NJ,Williams BR,Knolle P,Kneillin

    更新日期:2014-02-01 00:00:00

  • Critical functions for c-Myb at three checkpoints during thymocyte development.

    abstract::The transcription factor c-Myb is expressed throughout T cell development in the thymus. However, little is understood about c-Myb function because of the embryonic lethality of traditional Myb-null mutations. Using tissue-specific deletion to abrogate c-Myb expression at distinct stages of T cell development, we iden...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni1085

    authors: Bender TP,Kremer CS,Kraus M,Buch T,Rajewsky K

    更新日期:2004-07-01 00:00:00

  • Metabolic pressure and the breach of immunological self-tolerance.

    abstract::The prevalence of autoimmune disorders in affluent countries has reached epidemic proportions. Over the past 50 years, a reverse trend between the frequency of infectious diseases and the incidence of autoimmune and allergic diseases led to the so-called 'hygiene hypothesis'. Given the epidemiological evidence and rec...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.3851

    authors: De Rosa V,La Cava A,Matarese G

    更新日期:2017-10-18 00:00:00

  • A critical function for transforming growth factor-beta, interleukin 23 and proinflammatory cytokines in driving and modulating human T(H)-17 responses.

    abstract::Interleukin 17 (IL-17)-producing T helper 17 cells (T(H)-17 cells) have been described as a T helper cell subset distinct from T helper type 1 (T(H)1) and T(H)2 cells, with specific functions in antimicrobial defense and autoimmunity. The factors driving human T(H)-17 differentiation remain controversial. Using a syst...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.1613

    authors: Volpe E,Servant N,Zollinger R,Bogiatzi SI,Hupé P,Barillot E,Soumelis V

    更新日期:2008-06-01 00:00:00

  • Deletion of a coordinate regulator of type 2 cytokine expression in mice.

    abstract::Mechanisms that underlie the patterning of cytokine expression in T helper (T(H)) cell subsets remain incompletely defined. An evolutionarily conserved approximately 400-bp noncoding sequence in the intergenic region between the genes Il4 and Il13, designated conserved noncoding sequence 1 (CNS-1), was deleted in mice...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni0901-842

    authors: Mohrs M,Blankespoor CM,Wang ZE,Loots GG,Afzal V,Hadeiba H,Shinkai K,Rubin EM,Locksley RM

    更新日期:2001-09-01 00:00:00

  • Remote control of γc expression by arginine methylation.

    abstract:: ...

    journal_title:Nature immunology

    pub_type: 评论,杂志文章

    doi:10.1038/s41590-018-0240-x

    authors: Park JY,Park JH

    更新日期:2018-11-01 00:00:00

  • NLRX1 promotes immediate IRF1-directed antiviral responses by limiting dsRNA-activated translational inhibition mediated by PKR.

    abstract::NLRX1 is unique among the nucleotide-binding-domain and leucine-rich-repeat (NLR) proteins in its mitochondrial localization and ability to negatively regulate antiviral innate immunity dependent on the adaptors MAVS and STING. However, some studies have suggested a positive regulatory role for NLRX1 in inducing antiv...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.3853

    authors: Feng H,Lenarcic EM,Yamane D,Wauthier E,Mo J,Guo H,McGivern DR,González-López O,Misumi I,Reid LM,Whitmire JK,Ting JP,Duncan JA,Moorman NJ,Lemon SM

    更新日期:2017-12-01 00:00:00

  • Author Correction: At the end of the beginning: immunotherapies as living drugs.

    abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

    journal_title:Nature immunology

    pub_type: 已发布勘误

    doi:10.1038/s41590-019-0476-0

    authors: Feigal EG,DeWitt ND,Cantilena C,Peck C,Stroncek D

    更新日期:2019-10-01 00:00:00

  • Publisher Correction: Tet2 and Tet3 in B cells are required to repress CD86 and prevent autoimmunity.

    abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

    journal_title:Nature immunology

    pub_type: 已发布勘误

    doi:10.1038/s41590-020-00809-w

    authors: Tanaka S,Ise W,Inoue T,Ito A,Ono C,Shima Y,Sakakibara S,Nakayama M,Fujii K,Miura I,Sharif J,Koseki H,Koni PA,Raman I,Li QZ,Kubo M,Fujiki K,Nakato R,Shirahige K,Araki H,Miura F,Ito T,Kawakami E,Baba Y,Kuros

    更新日期:2020-12-01 00:00:00

  • A BATF-ling connection between B cells and follicular helper T cells.

    abstract::The transcription factor BATF directly regulates key components of the formation and function of follicular helper T cells and antibody class switching in B cells. ...

    journal_title:Nature immunology

    pub_type: 评论,新闻

    doi:10.1038/ni.2042

    authors: Ellyard JI,Vinuesa CG

    更新日期:2011-06-01 00:00:00

  • Nonmuscle myosin light-chain kinase mediates neutrophil transmigration in sepsis-induced lung inflammation by activating beta2 integrins.

    abstract::Nonmuscle myosin light-chain kinase (MYLK) mediates increased lung vascular endothelial permeability in lipopolysaccharide-induced lung inflammatory injury, the chief cause of the acute respiratory distress syndrome. In a lung injury model, we demonstrate here that MYLK was also essential for neutrophil transmigration...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.1628

    authors: Xu J,Gao XP,Ramchandran R,Zhao YY,Vogel SM,Malik AB

    更新日期:2008-08-01 00:00:00

  • The transcription factor BATF operates as an essential differentiation checkpoint in early effector CD8+ T cells.

    abstract::The transcription factor BATF is required for the differentiation of interleukin 17 (IL-17)-producing helper T cells (TH17 cells) and follicular helper T cells (TFH cells). Here we identified a fundamental role for BATF in regulating the differentiation of effector of CD8(+) T cells. BATF-deficient CD8(+) T cells show...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.2834

    authors: Kurachi M,Barnitz RA,Yosef N,Odorizzi PM,DiIorio MA,Lemieux ME,Yates K,Godec J,Klatt MG,Regev A,Wherry EJ,Haining WN

    更新日期:2014-04-01 00:00:00